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Ca²⁺ Redistribution from Bound to Free Form Is Required for Tumor Necrosis Factor Actions in 30A5 Preadipocytes

Department of Biochemistry, Purdue University West Lafayette, Indiana 47907
Department of Veterinary Physiology and Pharmacology, Purdue University West Lafayette, Indiana 47907

Address requests for reprints to: Dr. Ki-Han Kim, Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.

Abstract

Tumor necrosis factor/cachectin (TNF) inhibits differentiation of 30A5 preadipocytes into adipocytes. In this process, TNF inhibits the expression of the gene for acetyl-coenzyme-A carboxylase, the ratelimiting enzyme for biogenesis of long chain fatty acids. One of the early reactions caused by TNF is the Ca²⁺ redistribution of Ca²⁺ from the bound form to the free form. This Ca²⁺ redistribution results in a transient Ca²⁺ efflux. High concentrations of Mg²⁺ inhibit Ca²⁺ redistribution and efflux. This inhibition reverses the repression of acetyl-coenzyme-A carboxylase and reverses the TNF inhibition of the differentiation of 30A5 preadipocytes into adipocytes. This indicates that Ca²⁺ redistribution between the bound and the free form is an obligatory event in the sequence of actions caused by TNF in 30A5 cells.

FOOTNOTES

This is Journal Paper 12051 from the Agricultural Experimentation Station, Purdue University. This work was supported by NIH Grant CA-46882.

^* On leave from IL-YANG Pharmaceutical Industries Co., Ltd. (Seoul, Korea).

Received for publication March 8, 1990. Revision received July 19, 1990. Accepted for publication August 24, 1990.